Abstract: 【Abstract】 Objective To explore the effects of conventional hemodialysis (CHD), on-line hemodiafiltration (on-line HDF) and hemodialysis plus hemoperfusion (HD+HP) on clearance of medial molecular size substances and on improvement of restless legs syndrome (RLS). Methods The severity of RLS was graded following the diagnostic criteria of International Restless Legs Syndrome Study Group (IRLSSG) in patients with renal replacement therapy. Thirty cases with higher score were randomly and equally assigned to 3 treatment groups: A group (CHD 3 times/week), B group (CHD twice/week, and on-line HDF once/week), and C group (CHD twice/week and HD+HP once/week). The treatment lasted for 3 months. Serum iPTH and β2-microglobulin (β2m) were examined, and the change of RLS score was monitored. Results The changes of RLS score before and after the treatment were significant different among the 3 groups. Comparison of the scores showed that the decrease of score was significant between 2 groups, with the most remarkable decrease in C group followed by B group. The decrease of serum iPTH and β2m was significant in group A as compared with that in groups B and C, but was insignificant in group B as compared with that in group C. The decrease also showed no difference before and after the treatment in group A. Conclusion RLS in the patients can be improved by the 3 blood purification methods we used, among which HD+HP is most effective, followed by on-line HDF. CHD is no useful for the clearance of iPTH and β2m. On-line HDF and HD+HP have the same effect on clearance of medial molecular size substances.